James L Januzzi

Harvard Medical School, Boston, Massachusetts, United States

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Publications (79)562.68 Total impact

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    ABSTRACT: Arterial hypertension is a main determinant of arterial remodelling and atherosclerosis. Coronary artery calcium score and carotid intima-media thickness are recognized indices of vascular remodelling. Established biohumoral markers for the diagnosis of atherosclerosis are still lacking in asymptomatic subjects with hypertension. We aimed to test the association of plasma N-terminal pro B-type natriuretic peptide concentrations with either coronary artery calcium score or carotid intima-media thickness in asymptomatic hypertensive subjects. We conducted a case-control study on 436 hypertensi.ve and 436 age/sex-matched normotensive subjects from the population of the Montignoso HEart and Lung Project, a community-based study of asymptomatic general population ≥45 years. Subjects underwent N-terminal pro B-type natriuretic peptide measurement, echocardiography and evaluation of coronary artery calcium score and carotid intima-media thickness. Hypertensive subjects had higher median coronary artery calcium score (60 (interquartile range, 30-112) vs. 15 (interquartile range 3-70) Agatson units, p = 0.007), carotid intima-media thickness (8.6 (interquartile range 7.5-9.1) vs. 7.9 (7.1-8.4) µm, p < 0.001) and indexed left ventricular mass (101 (interquartile range 82-126) vs. 87 (63-91) mg/m2, p = 0.03) than controls, with no differences in left ventricular ejection fraction, diameters, E/E', left atrial area. N-terminal pro B-type natriuretic peptide concentrations were higher in hypertensive subjects with either coronary artery calcium score (p = 0.008) or carotid intima-media thickness >75th (p < 0.006) percentile and highest in combined coronary artery calcium score/carotid intima-media thickness >75th percentile (p = 0.021). In multivariable analysis, N-terminal pro B-type natriuretic peptide independently predicted either coronary artery calcium score or carotid intima-media thickness >75th percentile, but only in hypertensive subjects (odds ratio = 1.87, 95% confidence interval 1.30-2.74, p = 0.001 and odds ratio = 1.99, 95% confidence interval 1.43-2.76, p = 0.001). In asymptomatic subjects with hypertension, N-terminal pro B-type natriuretic peptide is a marker of hypertension-mediated preclinical vascular disease. © The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    European Journal of Preventive Cardiology 02/2015; DOI:10.1177/2047487315569675 · 2.68 Impact Factor
  • Domingo A Pascual-Figal, James L Januzzi
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    ABSTRACT: ST2 is a member of the Interleukin-1 receptor family with two main isoforms: transmembrane or cellular (ST2L) and soluble or circulating (sST2) forms. ST2 is the receptor of the IL-33, which is an IL-1 like cytokine that can be secreted by living cells in response to cell damage. IL-33 exerts its cellular functions by binding a receptor complex composed of ST2L and IL-1R accessory protein. The IL-33/ST2 system is up-regulated in cardiomyocytes and fibroblasts as response to mechanical stimulation or injury. The interaction between IL33 and ST2L has been demonstrated to be cardioprotective: in experimental models, this interaction reduces myocardial fibrosis, prevents cardiomyocyte hypertrophy, reduces apoptosis and improves myocardial function. The beneficial effects of IL-33 are specifically through the ST2L receptor. sST2 avidly binds IL-33 which results in interruption of the interaction between IL-33/ST2L and consequently eliminates the anti-remodeling effects; thus sST2 is viewed as a decoy receptor. In recent years, knowledge about ST2 role in the pathophysiology of cardiovascular diseases has broadly expanded, with strong links to myocardial dysfunction, fibrosis, and remodeling. Beyond its myocardial role, the IL-33/ST2 system could have an additional role in the development and progression of atherosclerosis. In conclusion, IL-33/ST2L signaling is a mechanically activated, cardioprotective fibroblast-cardiomyocyte paracrine system, which may have therapeutic potential for beneficially regulating the myocardial response to overload and injury. In contrast, sST2 acts as a decoy receptor and, by sequestering IL-33, antagonizes the cardioprotective effects of IL-33/ST2L interaction.
    The American Journal of Cardiology 01/2015; 115(7). DOI:10.1016/j.amjcard.2015.01.034 · 3.43 Impact Factor
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    ABSTRACT: sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF.
    PLoS ONE 10/2014; 9(10):e110976. DOI:10.1371/journal.pone.0110976 · 3.53 Impact Factor
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    ABSTRACT: No published information exists to support the safe use of ticagrelor in patients with a clopidogrel allergy. This study involved an institutional review board-approved retrospective review of patients with a documented clopidogrel allergy who subsequently received ticagrelor between July 2011 and February 2014. We report the cases of two patients with a history of hypersensitivity to clopidogrel in whom ticagrelor was used successfully without documented incident. In addition, principles suggesting a lack of cross-sensitivity between ticagrelor and clopidogrel are reviewed. These cases combined with theoretical evidence support the use of ticagrelor in patients with hypersensitivity to clopidogrel.
    Pharmacotherapy 08/2014; 34(8). DOI:10.1002/phar.1446 · 2.31 Impact Factor
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    ABSTRACT: Background Rehospitalization is a major cause for heart failure (HF) related morbidity, and is associated with considerable loss of quality of life and costs. The rate of unplanned rehospitalization in HF patients is unacceptably high; current risk stratification to identify patients at risk for rehospitalization is inadequate. We evaluated whether measurement of galectin-3 would be helpful in identifying patients at such risk. Methods We analyzed pooled data from patients (N=902) enrolled in 3 cohorts (COACH, N=592; PRIDE, N=181; and UMD H-23258, N=129) originally admitted because of HF. Mean patient age was between 61.6 and 72.9 years across the cohorts, with a wide range of left ventricular ejection fraction. Galectin-3 levels were measured during index admission. We used fixed and random effects models, as well as continuous and categorical reclassification statistics to assess the association of baseline galectin-3 levels with risk of post-discharge rehospitalization at different time points and the composite endpoint all cause mortality and rehospitalization. Results Compared to patients with galectin-3 concentrations below 17.8 ng/mL, those with results exceeding this value were significantly more likely to be rehospitalized for HF at 30, 60, 90 and 120 days after discharge; odds ratios (OR) 2.80 (95% CI: 1.41-5.57), 2.61 (95% CI: 1.46-4.65), 3.01 (95% 1.79-5.05) and 2.79 (95% 1.75-4.45), respectively. After adjustment for age, gender, NYHA class, renal function (eGFR), LVEF, and BNP, galectin-3 remained an independent predictor of HF rehospitalization. Addition of galectin-3 to risk models significantly reclassified patient risk of post-discharge rehospitalization and fatal event at each time point (continuous NRI at 30 days of +42.6% (95% CI: +19.9-65.4%), P <0.001). Conclusions Among patients hospitalized for HF, plasma galectin-3 concentration is useful for the prediction of near-term rehospitalization.
    American Heart Journal 06/2014; 167(6). DOI:10.1016/j.ahj.2014.02.011 · 4.56 Impact Factor
  • Parul U Gandhi, James L Januzzi
    European Heart Journal 05/2014; 36(6). DOI:10.1093/eurheartj/ehu211 · 14.72 Impact Factor
  • James L Januzzi, Paul J Hauptman
    Circulation Heart Failure 05/2014; 7(3):388-90. DOI:10.1161/CIRCHEARTFAILURE.114.001357 · 6.68 Impact Factor
  • Clinical Chemistry 04/2014; DOI:10.1373/clinchem.2014.223057 · 7.77 Impact Factor
  • International journal of cardiology 01/2014; 172(1). DOI:10.1016/j.ijcard.2013.12.129 · 6.18 Impact Factor
  • European Journal of Clinical Investigation 01/2014; · 3.37 Impact Factor
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    ABSTRACT: The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B-type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT-proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BNP and NT-proBNP relative to therapeutic intervention in HF has led to the concept of using the biomarkers as a 'guide' for intensification of HF care with a goal of not only achieving guideline-directed medical therapy goals accompanied by targeted natriuretic peptide suppression below prognostic thresholds. In studies achieving this combination of therapy optimization and BNP/NT-proBNP suppression, superior outcomes have been observed, and the approach was well tolerated. Natriuretic peptide-guided HF therapy has recently been given a recommendation in US HF guidelines to achieve guideline-directed medical therapy (Class IIa) and possibly improve outcome (Class IIb), while other clinical practice guidelines (including those from the European Society of Cardiology) await results from emerging clinical trial data. We will review lessons learned in the past regarding this novel concept of biomarker guided HF care, and discuss future directions for the approach.
    European Heart Journal 11/2013; 35(1). DOI:10.1093/eurheartj/eht463 · 14.72 Impact Factor
  • James L Januzzi, Roland Rj van Kimmenade
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    ABSTRACT: Following the introduction of B-type natriuretic peptide (BNP) and its amino-terminal equivalent (NT-proBNP), the use of biomarkers for the evaluation and management of heart failure (HF) has grown. Indeed, natriuretic peptide testing for diagnosis and prognosis recently earned a Class I Level of Evidence: A in the 2013 American Heart Association/American College of Cardiology clinical practice guidelines for HF (2). Although it took years to develop such support, this is indeed the proper recognition of the clinical role played by these important biomarkers.
    Journal of the American College of Cardiology 09/2013; 63(2). DOI:10.1016/j.jacc.2013.09.005 · 15.34 Impact Factor
  • Noreen P Kelly, James L Januzzi
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    ABSTRACT: OPINION STATEMENT: While heart failure (HF) treatment guidelines exist, there are significant gaps in their implementation owing in part to the lack of objective data to help guide clinicians in their medical decision-making. B-type natriuretic peptide (BNP) and its amino-terminal equivalent (NT-proBNP) are objective markers of HF prognosis, are useful to monitor response to treatment in outpatients with HF, and may have a role in "guiding" HF care as well. Successful BNP or NT-proBNP guided HF treatment requires regular attempts to reach and maintain target values (BNP ≤ 125 pg/mL or NT-proBNP ≤ 1000 pg/mL). This may be achieved through lifestyle modifications, exercise programs, medication adjustments, and therapeutic interventions shown to reduce morbidity and mortality in HF patients. Failure to achieve biomarker targets portends a worse prognosis, proportional to the lowest achieved natriuretic peptide concentration; in those with significant biomarker "nonresponse," prognosis is poor, and alternative therapeutic strategies should be considered.
    Current Treatment Options in Cardiovascular Medicine 05/2013; 15(4). DOI:10.1007/s11936-013-0247-4
  • James L Januzzi
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    ABSTRACT: Following the initial discovery of a natriuretic and diuretic peptide factor present in atrial myocardial tissue homogenates, subsequent elucidation of the natriuretic peptide (NP) family has led to substantial advances in the understanding of the autocrine, paracrine, and endocrine regulation of the cardiovascular system. Furthermore, with the development of assays for the measurement of the NPs, these important biomarkers have gone from being regarded as biological mediators of the cardiovascular system to now represent important clinical tools for the diagnostic and prognostic evaluation of patients with heart failure and may have potential as a therapeutic target in this setting as well. An historical perspective on the NPs from bench to bedside translation will be discussed.
    Journal of Investigative Medicine 05/2013; DOI:10.231/JIM.0b013e3182946b69 · 1.50 Impact Factor
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    ABSTRACT: BACKGROUND:: Soluble ST2 (sST2) is an emerging prognostic biomarker in patients with existing cardiovascular disease. ST2 and its ligand, interleukin-33 (IL-33), are expressed in endothelial cells, and may play an important role in the development of early atherosclerosis and vascular biology. We sought to investigate the association of sST2 and progression of blood pressure (BP), as well as the development of hypertension. METHODS:: Circulating sST2 concentrations were measured in 1834 participants (mean age 56 years, 57% women) of the community-based Framingham Offspring study. Participants were free of hypertension at baseline. Multivariable linear and logistic regression models were used to evaluate the association of sST2 concentrations and subsequent BP outcomes. RESULTS:: Higher sST2 concentrations were associated with incident hypertension over 3 years of follow-up [multivariable-adjusted odds ratio per 1 standard deviation increase in sST2 1.22, 95% confidence interval 1.05-1.42, P = 0.01]. Individuals in the upper sST2 quartile had a 2.6 mmHg greater increase in SBP compared with those in the lowest quartile (P for trend across quartiles 0.002) and a 1.8 mmHg greater increase in pulse pressure (P for trend 0.005). In contrast, sST2 concentrations were not associated with changes in DBP (P = 0.27). CONCLUSION:: These findings suggest that sST2 concentrations predict changes in BP physiology typically seen with aging and progressive arterial stiffness. Further studies are needed to elucidate underlying mechanisms by which the ST2/IL-33 pathway may contribute to BP physiology.
    Journal of Hypertension 04/2013; 31(7). DOI:10.1097/HJH.0b013e3283611bdf · 4.22 Impact Factor
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    ABSTRACT: Abstract Objective: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft vasculopathy and mortality after orthotopic heart transplantation (OHT). Methods: sST2 concentrations were measured in 241 patients following OHT. Results: Elevated sST2 was associated with cellular rejection (CR) ≥1R, with highest rates of CR in the 4th sST2 quartile (p = 0.003). No significant association between sST2 and antibody-mediated rejection or allograft vasculopathy was found. sST2 ≥30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01; 95% CI 1.15-3.51; p = 0.01). Conclusion: Concentrations of sST2 are associated with the presence of CR and predict long-term mortality following OHT.
    Biomarkers 04/2013; DOI:10.3109/1354750X.2013.773081 · 2.52 Impact Factor
  • James L Januzzi
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    ABSTRACT: ST2 is a member of the interleukin (IL)-1 receptor family discovered in a classical translational science fashion, and exists in two forms, a trans-membrane receptor (ST2L) as well as a soluble decoy receptor (sST2). The ligand of ST2 is IL-33, which is involved in reducing fibrosis and hypertrophy in mechanically strained tissues. In in vitro and in vivo models, ST2L transduces the effects of IL-33, while excess sST2 or abnormalities in ST2 signaling leads to cardiac hypertrophy, fibrosis, and ventricular dysfunction. Clinically, in patients with symptomatic heart failure (HF), elevated concentrations of sST2 are strongly associated with severity of the diagnosis, and powerfully predict increased risk of complications, independent of other established or emerging biomarkers. sST2 testing has also been shown to predict onset of symptomatic HF in patients with acute myocardial infarction, while in community-based subjects, sST2 values independently predict future HF, cardiovascular disease events, and mortality.
    Journal of Cardiovascular Translational Research 04/2013; 6(4). DOI:10.1007/s12265-013-9459-y · 3.06 Impact Factor
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    ABSTRACT: AIM: This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF). METHODS AND RESULTS: Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60mL/min/1.73m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2 (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). CONCLUSION: In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF.
    International journal of cardiology 03/2013; 168(3). DOI:10.1016/j.ijcard.2013.01.228 · 6.18 Impact Factor
  • James L Januzzi
    Journal of the American College of Cardiology 03/2013; DOI:10.1016/j.jacc.2013.01.039 · 15.34 Impact Factor
  • James L Januzzi, Richard Troughton
    Circulation 01/2013; 127(4):500-8. DOI:10.1161/CIRCULATIONAHA.112.120485 · 14.95 Impact Factor

Publication Stats

2k Citations
562.68 Total Impact Points


  • 2010–2015
    • Harvard Medical School
      • • Department of Medicine
      • • Department of Neurology
      Boston, Massachusetts, United States
  • 2009–2015
    • Massachusetts General Hospital
      • Division of Cardiology
      Boston, Massachusetts, United States
    • Odense University Hospital
      • Department of Cardiology - B
      Odense, South Denmark, Denmark
  • 2013
    • University of Murcia
      • Faculty of Medicine
      Murcia, Murcia, Spain
    • University of Otago
      Taieri, Otago Region, New Zealand
    • Boston University
      Boston, Massachusetts, United States
  • 2012–2013
    • University Medical Center Utrecht
      • Department of Cardiology
      Utrecht, Utrecht, Netherlands
    • University of Miami Miller School of Medicine
      • Division of Hospital Medicine
      Miami, FL, United States
    • University of Maryland, Baltimore
      • Division of Cardiology
      Baltimore, MD, United States
  • 2008–2013
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2011
    • University of Massachusetts Boston
      Boston, Massachusetts, United States